6,7-epoxygeranyl ethers of oxygen heterocyclic compounds

ABSTRACT

6,7-Epoxygeranyl ethers of the formula   WHEREIN N 0 TO 3 Y 5 or 6 membered divalent heterocyclic ring containing 1 oxygen atom and 1 sulfur atom in non-adjacent relationship and 3 or 4 carbon atoms; R hydrogen, alkyl, perchloroalkyl or alkoxy each of up to 4 carbons; and M 1 OR 2; ARE MODIFIERS OF INSECT GROWTH AND DEVELOPMENT.

United States Patent [1 1 Wat [ 6,7-EPOXYGERANYL ETHERS OF OXYGENHETEROCYCLIC COMPOUNDS [75] Inventor: Edward Koon Wah Wat,

Wilmington. Del.

[73] Assignee: E. I. du Pont de Nemours & Company, Wilmington. Del.

[22] Filed: Dec. 27, 1973 [2 l] App]. No.: 428,719

Related [1.8. Application Data [62] Division of Ser No. 23l,394, March2. 1972 Pat [52] US. Cl..... 260/240 R; 260/240 H; 260/327 M; 260/3409;260/3459; 260/347.8; 424/278; 424/285 [51] Int. Cl. C07d 327/04; C07d327/06 [58] Field of Search 260/240 R. 240 H, 327 M [56] ReferencesCited UNITED STATES PATENTS 3,701.75? l0/l972 Lee et al. n 260/327 M3,749 736 7/1973 Diekman 260/327 M 3,766.209 [0/1973 Emmick 3. 260/327 MJuly 22, 1975 Primary ExuminerArthur P. Demers Attorney, Agent. orFirmAnthony P. Mentis [57] ABSTRACT 6,7-Epoxygerzmyl ethers of theformula 2 Claims, No Drawings 6,7-EPOXYGERANYL ETHERS OF OXYGENHETEROCYCLIC COMPOUNDS This is a division, of application Ser. No.231,394, filed Mar. 2, 1972, now U.S. Pat. No. 3,823,162.

BACKGROUND OF THE INVENTION 1. Field of the Invention This inventionconcerns certain 6.7-epoxygeranyl ethers and their use to control thegrowth and development of harmful insects.

2. Prior Art Dutch patent application No. 69/l0,5l9 opened forinspection on Oct. 13, 1970, Bowers, US. Pat. No. 3,563,982, and Science164. 323 (1969). disclose certain aromatic ethers of 6,7-epoxygeraniolas insect control agents. They are not the same as the compounds of thisinvention.

DESCRIPTION OF THE INVENTION It has now been found that certain oxygenheterocyclic ethers, namely, 6,7-epoxygeranyl ethers of the formula gl(main-1M in which n is to 3;

The procedure of H. S. Hill et al. [.I. Am. Chem. Soc. 50, 2242 (1928)]was followed to obtain a mixture of2-methyl-4-hydroxymethyl-1,3-dioxolane and 2-methyl-S-hydroxy-1,3-dioxane. These were separated by converting thealcohol mixture to the benzoate derivative, using benzoyl chloride andpyridine. C rystallization from petroleum ether (30-60) gave a solidbenzoate, mp -85C., and an oily benzoate. There were numerousdifferences in the ir and nmr spectra.

Each ester was saponified with sodium hydroxide in water at 7()-80C. Thesolid benzoate gave rise to 2- methyl-S-hydroxy-1,3-dioxane. bp o4-65C10 mm); ir (film, 2.90 1. (OH); nmr (CECl 8 4.74 (q,1, .l 5. OCl-IM eO),3.92 (m, 4, CH O), 3.57 (m,2, CHOH), 1.31 (d,3, .I 5, CH

The liquid benzoate gave 2-methyl-4-hydroxymethyl- 1,3-dioxolane, bp78-83C. (10 mm); ir (film), 2.90;]. (OI-I); nmr (CDCl 5 4.9-5.3 (m,l,OCHMeO). 2.8-4.4 (m,6. CH O, CHOH), 1.3-1.5 (m.3, CH

Synthesis of intermediates in preparing the compounds of the variousexamples, as in Examples 10-19, is given herewith.

A. 2,2-Dimethyl-1,3-dioxolane-4-methanol (1).

Oil 4 Q,

a .on -o uo The preparation described in Organic Synthesis, Coll. Vol.III, p. 502 was modified slightly in that a Soxhlet extractor filledwith 3A molecular sieves was used to remove water. The product isexclusively dioxolane I, uncontaminated by isomeric dioxane. Yield 87%,bp 79-80 13 mm).

B. 2,2-Dimethyl-l,3-dioxolane-4-methyl Acetate (II) an QC r Ito-611 K "3QC M11 6 3 6 7- ox gereru'l. 2-nethy1- 2-nethy1- t(6,7- oxyln' tdiit-hydroxymethylgeranyloxymethyl 1, 3-d1oxo1ane 1 3-d1oxo1ane The alcoholI was acetylated as follows: Acetyl chloride g) was added over a periodof 1 hr to a solution of 254 g of the ketal l in 160 g of pyridine and750 ml of benzene while keeping the reaction mixture at 0-5 byice-cooling. After 3 hr at 0, the mixture was filtered and the solidswere promptly washed with benzene. The filtrate was concentrated and theresidual oil was distilled to give 321 g of liquid, bp 79-8 1 1 1 mm),96% yield; IR (film) 5.74 p. (C=O)', nmr

(CDCl 5 3.5-4.4 (m, 5, CH O, CH0), 2.03 (s, 3, CH CO), 1.39, 1.31 (25,6, CH

3 C. Z-t-Butyl-l.3-dioxolane-4-methyl Acetate (lll) o o 11+ n cl eo+ciio-+ ew 5 I! III The following is an example of the exchange reactionwhich has been used with a number of aldehydes to give dioxolanes suchas III.

A mixture of 19.1 g of the acetate ll. 35 g of pivaldehyde. 0.5 g ofp-toluenesulfonic acid hydrate, and 100 ml of benzene was refluxed for 5hr. The solution was washed with satd sodium bicarbonate solution. driedover potassium carbonate, and distilled to give 18.4 g (83% yield) ofliquid. bp 97-98 (11 mm). ir (film) 571 p. (C=O)'. nmr (CDClal'. 5 4.67.4.59 [25. l (cis. trans). OCHtBuOl. 3.6-4.3 (m, 5. CH CH0). 2.10 (s. 3.CH CO), 0.921s. 9. C(CH D. 2-t-Butyl-1.3-dioxolane-4-methanol (1V) sumThe acetate group can be removed by basic hydrolysis but the hydridereduction procedure is preferred because non-aqueous work-up is used.

To a suspension of 2.0 g of lithium aluminum hydride in 50 ml of THF wasadded 16.5 g of the acetate 11] at 0-10. After 30 min at 0, 2.0 ml ofwater is cautiously added. followed by 2.0 ml of 15% aq. sodiumhydroxide. and 6.0 ml of water. The solids were removed by filtrationand were thoroughly washed with ether. Distillation of the filtrate gave1 1.6 g of liquid. bp 87-89 (11 mm). 89% yield. IR (film) 2.94;; (OH);NMR (CDCI 2s(lH) 4.69. 4.60 8 (OCHtBuO); m(5H) 3.5-4.3 (CH-,0, CHO);m(lH) 2.7 (OH); 5(9H) 0.96

The above sequence was applied to the examples in which the2-substituent was: iso-butyl. sec-butyl. tbutyl. diethyl. ethyl. andalso to the oxathiolane example where the starting material was3-mercaptopropan-l .2-diol.

SPECIFIC EMBODIMENTS OF THE INVENTION In the following examples. whichare illustrative and not limitative. all parts and percentages are byweight unless specified otherwise.

EXAMPLE 1 2-Methyl-4(6.7-epoxygeranyloxymethyl)-1.3- dioxolane To asolution of 9.4 g (80 mmol) of 2-methyl-4- hydroxymethyl-l.3-dioxolanein 50 ml of tetrahydrofuran (THF) at 70C was added 50 ml of 1.6Msolution of n-hutyllithium in hexane. The mixture was stirred at C for15 minutes and then 16.0 g of crude 6.7-epoxygeranyl bromide was added.The mixture was stirred at 25C for 22 hours and at 50C for 4 hours. Thereaction mixture was poured into water and the product extracted intoether. The combined ether extracts were dried over potassium carbonateand concentrated under reduced pressure. Partial evaporativedistillation at 70C/0.2 mm yielded some unreacted epoxygeranyl bromide.Further distillation at 90C/0.02 mm gave 5.61 g of 2-methyl-4-(6.7-epoxygeranyloxymethyl)-1.3-dioxo1ane: ir (film) 5.9511 (C=C). 11.5 1.(epoxide); nmr (CDCl '6 5.43 (m,1. vinyl). 5.10 (m. l. OCflCH O).3.7-4.3 (m.5. CH O. CHO). 3.3-3.6 (m.2. CH O). 2.7 (t.1, 6. epoxide H).2.0-2.4 (m.2. allylic CH 1.71 (m.5, allylic CH3. epoxidc CH 1.2-1.5(m,9. epoxide CH OCCH O); tlc, single spot on silica gel. 3:1benzene:ether.

EXAMPLE 2 2-(6.7-Epoxygeranyloxymethyl) tetrahydrofuran EXAMPLE 32-Ethyl-4-( 6.7-epoxygeranyloxymethyl) l .3-dioxolane The procedure ofExample 1 was applied to 10.6 g mmol) of2-ethyl-4-hydroxymethyl-1.3-dioxolane in place of the 2-methy1 homolog.In addition. 10 ml of hexamethylphosphoramide was used as cosolvent andno heating was required. The product, 5.7 g of Z-ethyl-4-(6.7-epoxygeranyloxymethyl)- l .3-dioxolane. was obtained byevaporative distillation at 1 15C (0.04 mm); ir (film), 6.00;). (C=C)'.11.5 (epoxide); nmr (CDCl,). 8 5.41 (m,1, vinyl H); 4.9 (m,1. OCHEtO);3.3-4.3 (m,7, CH,O, CH0); 2.69 (t,l,.l 7. epoxide H); 1.27. 1.22 (25.6.epoxide CH 0.92 (t.3, .l 7. CH

Using the procedure of Example l the following heterocyclic alcoholswere reacted with 6.7-epoxygeranyl bromide under the conditions shown togive compounds of the invention wherein the values for n. Y and R are asindicated.

a c n,

S 6 TABLE I Distillation m Rommel et .l. -l "Dims-lwdrow-z-etmrl-l,3410mm: 120 [0.03 2m) a (1:3, 1.

no 1- dro at 1-2 2-diucthyl- 100 (0.0 m) 1' (can, 2 5 CH: L I (CH3). bgdio ian o E 6 H0 J-liydroawtetrnhydrumran (0.0" In) 0 U H 1 7 BOOM-Ul-Hydromettwl-lJ-dioxolane (0.07 mm) 1 {-3 It 1 a no?S-Hydrwqr-lJ-dioxsno 105 (0.0 mi) 0 f a 1 HOIQHfla-U z-(a-ioaro m imtmmrw 120 0.05 mm) 3 U u 1 10 H008; B-Hydromethyl-Z-isopropyl- 115 (0.05m) 1 0 5-0 8 1 I OI lJ-dioxolane I I o} 11 B0 15-Bydrmry-2-1sepropyl-l,B-dioxane 120 (0.03 m) 0 0 L4, 1 con-g a 12KOCH; l-llydromethyl-z -trichloto- 125 (0.0008 mm) 1 061: 1

I u methyl-1 3 -dioxo1anu 1} "00H; fl-lwdrmqrmethyl-prcpyl- (0.03 mm) 1T 51 0,31 1

H n lJ-dioxolane C 1- 1 HO CH 8- 2- d at 1 4t 1- 110 0.00 m) 2 C 3, 1

( a): gg ggiy W 3 9 Oi 15 KOCH: LBydrometlwI-bgq-butyl- (0.0} m) J. E-?HCfl-t, 1

I I mega, Lj-dioxolane ca:

I H: 16 KOCH ldrcmetlw -2-1sc'buty1- 115 0.0} an 1 I 5 CH Cflclh): 1 a Ij bg dioxolane o CH CIKCH 17 HOUR 'ldro ethyl-btett-butyl- 110 0.0} m 1C Cl-L 1 2 I di Lg diofiane L01 )3 18 HOClfgU 2-ttydromeuwl-5-ethyl-runn115 (0.0} In) 1 U- 6 1 I Ca s 9 R008; dlvdroaqmethy 4,241: n: a a 1 a 1m 115 (o o; 1 a

I I lJ-dloxolane i ia): 0

20 men, s-mdrcmetwl-i -ewl- (0.03 m) 1 cm, 1

I. *c 1,3-onth1o1ana The compounds of the invention have activity asjuvenile hormone mimics in certain harmful insects and therefore haveutility as insect control agents.

Tenebrio (yellow mealworm assay). Tenebrio molitor is a beetle whichinfests stored grain and is a commonly used test species. The compoundis dissolved in ace tone and the solution is applied to the abdomen of ayoung pupa from which the adult insect develops. The ED is the amount ofcompound necessary to severely deform half of the test animals used.These insects will not live or reproduce.

Aeries aegypn' (mosquito). The compound is dissolved or suspended inwater and newly hatched larvae are reared in the medium. Suppression ofadult emergence is the criterion of activity. The EC is the concentrathesame type of purpose. The additives used can be ortion at which only 50%of the larvae emerge as adults. ganic solvents, such as sesame oil,solvents of the xy- Biological activity is given in Table ll. lene type.petroleum fractions, etc.; water; emulsifiers; surfactantsftalcum',pyrophyllite, kieselguhr, gypsum TABLE II and/or clay; propellants suchas dichlorodifluoromethane. etc. The concentration of active mate-Compound of rial in such preparations can vary within wide limits, butin general should not be much higher than about l (H1053 pg Granaryweevil llllfl control at based on the total welght of the PreparationPnaf PP T hchtlc H) erahlv the concentration should be about Oil toabout K8 contro at lllllll ppm 2 12 #g Granary weevil 777' control at10% by of the total} P F I moo ppm. confused flour beetle Theembodiments of the invention In which an exclusiv ro rt or rivile e isclaimed are defined as f 3 (M10066 pg Mosquito-E43 (1.75 ppm; Granary ep pe y p g 01 weevil lllll7: control at IUUU ppm; lOWSZcprrtpsxglflflour beetle 94% control 5 L A compound of the formula 4onus 1.1g 5 (H2 pg (iranur wee\il llllY/l control at lllUU ppm; confusedflour beetle 94% control at llllll) ppm n so pg 7 St] 0(CH Y-R 8 13 ,ug*4 lil pg O Ill (Hull 3 pg Mosquito EC. 0.62 ppm 1 1 (H156 Mg 1: 0.42 gI} 0.018 pg Mosquito E11,: 0.37 ppm r l4 3.5 u 7 nlsOto 3; t

Y IS a 5- or 6-membered divalent ring having I atom I7 is: ag of oxygenand 1 atom of sulfur in non-adjacent reso i 'fi latlonship and 3 or 4carbon atoms; (W65 as R is hydrogen, alkyl, perchloroalkyl or alkoxyeach havltng up to 4 carbon atoms; and

m IS

Insecticidal compositions can be prepared by mixing an effective amountof one or more of the compounds in a suitable carrier depending on theparticular mode of application. They can be made up in various formscustomary in insect pest control, such as emulsions. 1 Y o 2. Thecompound of claim 1 in which suspensions, solutions. powders andaerosols. ln general, such preparations can in addition to the activeingredient contain the customary auxiliary agents. The

compound according to the invention can be the only R=C H2-ethyl-5-(6,7-epoxygeranyloxymethyl)l ,3- active ingredient. but can beprocessed also together 40 oxathiolane.

with one or more other agents which have more or less

1. A COMPOUND OF THE FORMULA
 2. The compound of claim 1 in which n 1,